Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations

Detalhes bibliográficos
Autor(a) principal: Coelho, Millene Borges
Data de Publicação: 2011
Outros Autores: Dalla Costa, Elis Regina, Vasconcellos, Sidra Ezídio Gonçalves, Linck, Natali, Ramos, Ricardo Martins, Amorim, Hermes Luís Neubauer de, Suffys, Philip Noel, Santos, Adalberto Rezende, Silva, Pedro Eduardo Almeida da, Ramos, Daniela Fernandes, Silva, Márcia Susana Nunes, Rossetti, Maria Lucia Rosa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/17633
Resumo: Acesso aberto na Internet Janeiro 2017
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spelling Coelho, Millene BorgesDalla Costa, Elis ReginaVasconcellos, Sidra Ezídio GonçalvesLinck, NataliRamos, Ricardo MartinsAmorim, Hermes Luís Neubauer deSuffys, Philip NoelSantos, Adalberto RezendeSilva, Pedro Eduardo Almeida daRamos, Daniela FernandesSilva, Márcia Susana NunesRossetti, Maria Lucia Rosa2017-01-31T13:02:48Z2017-01-31T13:02:48Z2011COELHO, Millene Borges; et al. Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: Identification of new mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, v.712, n.1–2, p.33–39, July 2011.0027-5107https://www.arca.fiocruz.br/handle/icict/1763310.1016/j.mrfmmm.2011.03.017Acesso aberto na Internet Janeiro 2017Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Fundação Estadual de Produção e Pesquisa em Saúde. Centro de Desenvolvimento Científico e Tecnológico (CDCT/FEPPS). Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada em Micobactérias. Rio de Janeiro, RJ. Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada em Micobactérias. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada em Micobactérias. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio Grande do Sul. Faculdade de Medicina. Laboratório de Micobactéria. Porto Alegre, RS, Brasil.Universidade Federal do Rio Grande do Sul. Faculdade de Medicina. Laboratório de Micobactéria. Porto Alegre, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil / Fundação Estadual de Produção e Pesquisa em Saúde. Centro de Desenvolvimento Científico e Tecnológico (CDCT/FEPPS). Porto Alegre, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil / Fundação Estadual de Produção e Pesquisa em Saúde. Centro de Desenvolvimento Científico e Tecnológico (CDCT/FEPPS). Porto Alegre, RS, Brasil.The present study was carried out to investigate the presence of polymorphism in the N-acetyltransferase gene of 41 clinical isolates of Mycobacterium tuberculosis, that were resistant to isoniazid (INH) with no mutations in the hot spots of the genes previously described to be involved in INH resistance (katG, inhA and ahpC). We observed single nucleotide polymorphisms (SNPs) in ten of these, including the G619A SNP in five isolates and an additional four so far un-described mutations in another five isolates. Among the latter SNPs, two were synonymous (C276T, n=1 and C375G, n=3), while two more non-synonymous SNPs were composed of C373A (Leu→Met) and T503G (Met→Arg) were observed in respectively one and two isolates. Molecular modeling and structural analysis based in a constructed full length 3D models of wild type TBNAT (TBNAT_H37Rv) and the isoforms (TBNAT_L125M and TBNAT_M168R) were also performed. The refined models show that, just as observed in human NATs, the carboxyl terminus extends deep within the folded enzyme, into close proximity to the buried catalytic triad. Analysis of tbnat that present non-synonymous mutations indicates that both substitutions are plausible to affect enzyme specificity or acetyl-CoA binding capacity. The results contribute to a better understanding of structure-function relationships of NATs. However, further investigation including INH-sensitive strains as a control group is needed to get better understanding of the possible role of these new mutations on tuberculosis control.engElsevierMycobacterium tuberculosisResistência a medicamentosModelagem molecularEstrutura-funçãoMutaçãoMutationStructure–functionDrug resistanceMolecular modelingMycobacterium tuberculosisSequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
title Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
spellingShingle Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
Coelho, Millene Borges
Mycobacterium tuberculosis
Resistência a medicamentos
Modelagem molecular
Estrutura-função
Mutação
Mutation
Structure–function
Drug resistance
Molecular modeling
Mycobacterium tuberculosis
title_short Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
title_full Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
title_fullStr Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
title_full_unstemmed Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
title_sort Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
author Coelho, Millene Borges
author_facet Coelho, Millene Borges
Dalla Costa, Elis Regina
Vasconcellos, Sidra Ezídio Gonçalves
Linck, Natali
Ramos, Ricardo Martins
Amorim, Hermes Luís Neubauer de
Suffys, Philip Noel
Santos, Adalberto Rezende
Silva, Pedro Eduardo Almeida da
Ramos, Daniela Fernandes
Silva, Márcia Susana Nunes
Rossetti, Maria Lucia Rosa
author_role author
author2 Dalla Costa, Elis Regina
Vasconcellos, Sidra Ezídio Gonçalves
Linck, Natali
Ramos, Ricardo Martins
Amorim, Hermes Luís Neubauer de
Suffys, Philip Noel
Santos, Adalberto Rezende
Silva, Pedro Eduardo Almeida da
Ramos, Daniela Fernandes
Silva, Márcia Susana Nunes
Rossetti, Maria Lucia Rosa
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Coelho, Millene Borges
Dalla Costa, Elis Regina
Vasconcellos, Sidra Ezídio Gonçalves
Linck, Natali
Ramos, Ricardo Martins
Amorim, Hermes Luís Neubauer de
Suffys, Philip Noel
Santos, Adalberto Rezende
Silva, Pedro Eduardo Almeida da
Ramos, Daniela Fernandes
Silva, Márcia Susana Nunes
Rossetti, Maria Lucia Rosa
dc.subject.other.pt_BR.fl_str_mv Mycobacterium tuberculosis
Resistência a medicamentos
Modelagem molecular
Estrutura-função
Mutação
topic Mycobacterium tuberculosis
Resistência a medicamentos
Modelagem molecular
Estrutura-função
Mutação
Mutation
Structure–function
Drug resistance
Molecular modeling
Mycobacterium tuberculosis
dc.subject.en.pt_BR.fl_str_mv Mutation
Structure–function
Drug resistance
Molecular modeling
Mycobacterium tuberculosis
description Acesso aberto na Internet Janeiro 2017
publishDate 2011
dc.date.issued.fl_str_mv 2011
dc.date.accessioned.fl_str_mv 2017-01-31T13:02:48Z
dc.date.available.fl_str_mv 2017-01-31T13:02:48Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv COELHO, Millene Borges; et al. Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: Identification of new mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, v.712, n.1–2, p.33–39, July 2011.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/17633
dc.identifier.issn.pt_BR.fl_str_mv 0027-5107
dc.identifier.doi.none.fl_str_mv 10.1016/j.mrfmmm.2011.03.017
identifier_str_mv COELHO, Millene Borges; et al. Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: Identification of new mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, v.712, n.1–2, p.33–39, July 2011.
0027-5107
10.1016/j.mrfmmm.2011.03.017
url https://www.arca.fiocruz.br/handle/icict/17633
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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